Cleophas T J, Niemeyer M C, van der Wall E E, van der Meulen J
Department of Medicine, University Hospital Groningen, The Netherlands.
Angiology. 1996 Jul;47(7):679-85. doi: 10.1177/000331979604700707.
Nitrates, although important for the management of angina pectoris, cause significant headache in many patients.
In a randomized, double-blind, crossover study, 89 patients with stable angina pectoris were studied to compare two different dosage strategies of isosorbide-5-mononitrate (5-ISMN). Patients were randomized to either 60 mg 5-ISMN once daily (od) for two weeks or to 30 mg 5-ISMN od for one week followed by 60 mg 5-ISMN od for one week. Then, there was a two-week placebo washout, after which the alternative treatment was given. The authors assessed the occurrence of angina pectoris and headache by diary cards while taking into account the number of isosorbide dinitrate sublingual puffs and paracetamole tablets required. Data were assessed for carryover and time effects.
The two dosage regimens were equally efficient for the relief of angina pectoris without development of tolerance. Thirty percent of the patients never experienced headache from the given dosages. In the remainder of them there was a highly significant time effect: the overall numbers of headache attacks in the first period of active treatment versus the second were 2,380 vs 1,400 (P < 0.003). Yet significantly fewer patients had headache on low dosage than on high dosage (45 vs 57, P < 0.02).
(1) Starting on a low dosage was associated with a reduced frequency and severity of headache and did not notably influence the beneficial effect on angina pectoris. (2) One in 3 patients never experienced headache from the given dosages. (3) The overall number of headache attacks in the first period of active treatment was significantly higher than in the second period irrespective of the dosages given.
硝酸盐类药物尽管对心绞痛的治疗很重要，但会使许多患者出现严重头痛。
在一项随机、双盲、交叉研究中，对89例稳定型心绞痛患者进行研究，以比较5-单硝酸异山梨酯（5-ISMN）的两种不同给药策略。患者被随机分为两组，一组每天服用60 mg 5-ISMN，持续两周；另一组先每天服用30 mg 5-ISMN，持续一周，然后每天服用60 mg 5-ISMN，持续一周。之后，有两周的安慰剂洗脱期，然后给予替代治疗。作者通过日记卡评估心绞痛和头痛的发生情况，同时考虑所需的硝酸异山梨酯舌下含片和对乙酰氨基酚片的数量。对数据进行了残留效应和时间效应评估。
两种给药方案在缓解心绞痛方面同样有效，且未产生耐受性。30%的患者从未因给定剂量出现头痛。在其余患者中，存在高度显著的时间效应：积极治疗的第一阶段与第二阶段的头痛发作总数分别为2380次和1400次（P < 0.003）。然而，低剂量组头痛的患者明显少于高剂量组（45例对57例，P < 0.02）。
（1）起始剂量较低与头痛频率和严重程度降低相关，且对心绞痛的有益作用无显著影响。（2）三分之一的患者从未因给定剂量出现头痛。（3）无论给予何种剂量，积极治疗的第一阶段头痛发作的总数均显著高于第二阶段。
